Experiments have been performed that demonstrate an active non- specific immunosuppressive factor(s) in human cord blood and in the serum of rats transplanted with Morris Hepatoma 7777. The factor appears to be concentrated in the fractions containing the highest concentration of alpha1-fetoprotein (AFP). These fractions inhibit in vitro human and rat lymphocyte cultures stimulated by phytohemagglutinin (PHA), pokeweed and allogeneic lymphocytes. Acting on the hypothesis that AFP may be an immunoregulatory protein, in vitro and in vivo studies have been performed to determine: 1) whether the active factor is AFP or, if not, what is it?; 2) what is the mechanism(s) of action?; 3) what is the biologic significance of the material? Fractionation experiments including isolation of AFP of greater than 90 percent purity have failed to confirm the original hypothesis and the active principle in both serum of rats bearing hepatoma 7777 and human cord blood appears to dissociate from the fetoprotein. Current experiments have been designed to confirm or refute this observation employing other isolation techniques and to better identify, if possible, the active fraction.